Utility of low-dose oral aspirin challenges for diagnosis of aspirin-exacerbated respiratory disease

Abstract

Background: Aspirin-exacerbated respiratory disease (AERD) is diagnosed through graded aspirin challenges that induce hypersensitivity reactions and eicosanoid level changes. It is not known whether diagnostically useful changes also occur after low-dose aspirin challenges that do not induce hypersensitivity reactions.

Objective: To investigate the utility of low-dose oral aspirin challenges for diagnosing AERD by measuring different clinical parameters and eicosanoid changes.

Methods: Sixteen patients with AERD and 13 patients with aspirin-tolerant asthma underwent oral challenges with low-dose (20 or 40 mg) aspirin and diagnostic oral graded aspirin challenges (up to 325 mg of aspirin). Forced expiratory volume in 1 second, nasal peak flow, the fraction of exhaled nitric oxide (FeNO), and eicosanoid levels in plasma and urine were analyzed.

Results: In patients with AERD but not in those with aspirin-tolerant asthma, 40-mg aspirin challenges induced a significant mean (SEM) decrease from baseline in FeNO (19% [5.1%]; P = .001) without causing any hypersensitivity reaction. The FeNO decrease also occurred after higher-dose aspirin challenges (27.8% [4.9%]; P < .001). The sensitivity and specificity of 40-mg aspirin-induced FeNO changes for identifying AERD were 90% and 100% with an area under the curve of 0.98 (95% CI, 0.92-1.00). The low-dose challenge also induced a significant leukotriene E4 urine increase in patients with AERD (from 6.32 [0.08] to 6.91 [0.15] log-pg/mg creatinine; P < .001), but the sensitivity and specificity of these changes were less than for the FeNO changes.

Conclusion: The low-dose aspirin-induced decrease in FeNO in patients with AERD may be useful for the diagnosis of aspirin allergy without inducing a hypersensitivity reaction.

Trial registration: clinicaltrials.gov Identifier: NCT01320072.

Conflict of interest statement

Conflict of interest:

Dr. Elina Jerschow holds an Investigator Initiated Research Award IISP39161 from Merck & Co., Inc. Other authors have no potential conflict of interest

Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

FeNO change after 40 mg aspirin challenge. 1a. In AERD patients (N=14), there was a significant decrease in FeNO (p=0.001). 1b. In ATA patients (N=10), there was no significant change in FeNO (p=0.08). Gray thin lines represent individual data points. Red thicker lines represent mean values.

Figure 2

FeNO change after standard oral graded aspirin challenge. 2a. In AERD patients (N=16), there was a significant decrease in FeNO (p<0.001). 2b. In ATA patients (N=10), there was no significant change in FeNO (p=0.1). Gray thin lines represent individual data points. Red thicker lines represent mean values.

Figure 3

FEV1 and NPF change after 40 mg aspirin and after standard oral graded aspirin challenge. 3a and 3c. In AERD patients after 40 mg aspirin challenge, there was no significant decrease in FEV1 or in NPF. There was a significant decrease in FEV1 (p=0.03) and in NPF (p=0.001) after graded aspirin challenge. 3b and 3d. In ATA patients there was no significant change in FEV1 or in NPF after 40 mg aspirin or after graded aspirin challenge.

Figure 3

FEV1 and NPF change after 40 mg aspirin and after standard oral graded aspirin challenge. 3a and 3c. In AERD patients after 40 mg aspirin challenge, there was no significant decrease in FEV1 or in NPF. There was a significant decrease in FEV1 (p=0.03) and in NPF (p=0.001) after graded aspirin challenge. 3b and 3d. In ATA patients there was no significant change in FEV1 or in NPF after 40 mg aspirin or after graded aspirin challenge.

Figure 4

Change in LTE4 urine levels after low and standard oral graded aspirin challenge. 4a. After 20 mg aspirin challenge there was no significant change in LTE4 levels in either group. In AERD patients after 40 mg aspirin challenge, there was a significant increase in LTE4 levels (p=0.001). 4b. There was a significant increase in urinary LTE4 levels after standard graded aspirin challenge in AERD and in ATA patients (p<0.001 and p=0.02, respectively).

Figure 5

Change in tetranor PGDM urine levels after low and standard oral graded aspirin challenge. 5a. After low-dose aspirin challenge there was no significant change in tetranor PGDM levels in either group. 6b. After standard graded aspirin challenge, there was a significant increase in tetranor PGDM levels in AERD patients with FEV1 decrease of ≥20% (n=10, p=0.001). There was a decrease in tetranor PGDM levels in AERD patients with FEV1 decrease of <20% (n=6), and in ATA patients (n=13), (p=0.02 and p<0.01, respectively).

Figure 6

Receiver operating characteristic (ROC) curves for FeNO change (6a.) and urinary LTE4 change (6b.) after 40 mg aspirin challenge.